Authors:
Shay Porat, Noa Weinberg-Corem, Sharona Tornovsky-Babaey, Rachel Schyr-Ben-Haroush, Ayat Hija, Miri Stolovich-Rain, Daniela Dadon, Zvi Granot, Vered Ben-Hur, Peter White, Christophe A. Girard, Rotem Karni, Klaus H. Kaestner, Frances M. Ashcroft, Mark A. Magnuson, Ann Saada, Joseph Grimsby, Benjamin Glaser, & Yuval Dor
Summary:
Recent studies revealed a surprising regenerative capacity of insulin-producing β cells in mice, suggesting that regenerative therapy for human diabetes could in principle be achieved. Physiologic β cell regeneration under stressed conditions relies on accelerated proliferation of surviving β cells, but the factors that trigger and control this response remain unclear. Using islet transplantation experiments, we show that β cell mass is controlled systemically rather than by local factors such as tissue damage. Chronic changes in β cell glucose metabolism, rather than blood glucose levels per se, are the main positive regulator of basal and compensatory β cell proliferation in vivo. Intracellularly, genetic and pharmacologic manipulations reveal that glucose induces β cell replication via metabolism by glucokinase, the first step of glycolysis, followed by closure of KATP channels and membrane depolarization. Our data provide a molecular mechanism for homeostatic control of β cell mass by metabolic demand.
Source:
Cell Metabolism; Vol. 13, Issue 4, 440-449 (04/06/11)